PARP (poly ADP-ribose polymerase) inhibitors with a phthalazinone structure are known, in particular as BER (base excision repair) inhibitors. WO 2005/053662 discloses the use of said inhibitors for the treatment of tumor cells with an HR (homologous recombination) dependent DNA DSB (double-strand break) repair deficiency. In particular it describes the use of said compounds for tumors presenting a deficiency of phenotype BCRA1 and/or BCRA2, such as ovarian, breast or prostate cancer.
Olaparib (4-[3-(4-cyclopropanecarbonyl-piperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin-2-one), described in U.S. Pat. No. 7,449,464, is a PARP inhibitor used in the treatment of tumors, in combination with radiotherapy or chemotherapy.
Two crystalline forms of Olaparib, defined as form A and form L, are known in the literature. A solvated form of form A is also known.
Form A is described in U.S. Pat. No. 8,247,416. The crystalline form A of Olaparib has an XRPD spectrum (λ=1.5418 Å) containing the most intense peaks at 2θ=10.5, 12.0, 14.0, 17.8, 21.1, 21.7, 22.3, 24.3, 26.1, 29.2.
The solvated crystalline form A, also described in U.S. Pat. No. 8,247,416, can be obtained by maturation and crystallization from different solvents. The XRPD spectrum (λ=1.5418 Å) of Olaparib as solvated form A has characteristic peaks at 2θ=7.0-7.5, 10.1-10.6, 15.1-15.6, 18.5-19.0, 21.0-21.5, 24.8-25.3, 27.0-27.5.
Form L, disclosed in US 2010/286157, has an XRPD spectrum (λ=1.5418 Å) containing the most intense peaks at 2θ=10.4, 13.6, 14.4, 17.2, 17.5, 18.8, 23.0, 25.1.
Particular crystalline forms of Olaparib can possess advantageous properties in terms of their solubility and/or stability and/or bioavailability and/or impurity profile and/or filtration characteristics and/or drying characteristics and/or their ability to be handled and/or micronized and/or preparation of solid oral forms.